Over the past decade, data have accumulated indicating that dopamine (DA) is retinal transmitter. The most suggestive data are the findings that specific neural cells in retina contain DA, and that the retina contains tyrosine hydroxylase; other data are less impressive. Serotonin (5HT) and norepinephrine (NE) may also be retinal transmitters, but only fragmentary information exists suggestive of this role in the mammalian retina. The first major aim of this research proposal is thus to determine, using biochemical and pharmacological approaches, whether 5HT and/or NE function as transmitters in the rat retina, and to obtain further data supportive of this role for DA. The second major aim is to study variations in retinal monoamine dynamics in relation to alterations in environmental lighting. The monoamine transmitters are synthesized from amino acids (tryptophan, tyrosine). For brain neurons, monoamine synthesis is known to depend in part on the availability of these amino acids from the circulation. Amino acid uptake into retina may be like that for brain (a competitive transport mechanism located at the blood-tissue barrier). If so, variations in amino acid levels in blood may lead to predictable changes in retinal tryptophan and tyrosine, and thus perhaps also in the synthesis and release of monoamines by retinal neurons. However, too few data exist dealing with the properties of the blood-retinal barrier concerning the transport of tryptophan and tyrosine. Hence, the third major aim of this application is to determine the mechanism(s) governing amino acid availability to the retina from the circulation, and their impact on retinal monoamine synthesis and turnover. The proposed studies focus primarily on in vivo experiments in the rat. However, selected studies will also be carried out in vitro, using retinal cultures. If successful, these experiments will help to establish, biochemically and pharmacologically, whether specific monoamines function as transmitters in the mammalian retina, and whether they might be involved in the processing of visual information by the retina. If so, then treatments that change the rates oif monoamine synthesis and turnover may ultimately be expected to influence vision. Such effects may one day be of therapeutic interest.